Case Presentation - Transplant and Hep C

Case presentation - transplant and hep c - shiny 12-1-15 from shinypharmacy

ACCP annual meeting 2015

Ambulatory Care Rotation - GI/Hepatology - Videos

Educational videos for nurses in the GI/hepatology clinic. 

Daklina

Viekira Pak

Grazoprevir/elbasvir

 

APPE - General Medicine Rotation - Drug Information Question

APhA ASP Webinar Series - International Vice Presidents 2015

My first webinar I presented to pharmacy students around the country to promote APhA-ASP, IPSF, and Public Health!

APPE - General Medicine Rotation - Case Presentation - Pancrealipase (Creon) use in Pancreatic Disorders

Pancrealipase (Creon) use in Pancreatic Disorders from shinypharmacy

APPE - General Medicine Rotation - Journal Club

APPE - General Medicine Rotation - Statin Guidelines Presentation for Physicians

APPE - Neurology Rotation - Idrarucizumab Drug Presentation for Physicians

APPE - Neurology Rotation - Drug Information Question

Does cardioversion with amiodarone in the setting of a recent stroke increase stroke risk? 

Should patient be anticoagulated prior to cardioversion?

Background:

Cardioversion is the electrical or chemical process of restoring the heart’s normal rhythm and is often utilized in atrial fibrillation patients who have abnormal heart rhythms originating in the atria. Cardioversion can help to improve cardiac function and control the symptoms of atrial fibrillation which can include no symptoms to rapid heartbeat, shortness of breath, or fatigue.  Electrical cardioversion is the synchronized process of delivering electrical current to the heart which causes the heart cells to contract simultaneously and terminate the abnormal rhythm after which the heart is able to restore a normal heart beat¹.  Atrial fibrillation can be treated using rate-controlling drugs such as beta blockers, calcium channel blockers, digoxin that allow atrial fibrillation to persist or rhythm control which can help to maintain sinus rhythm and can be implemented with drugs such as amiodarone, disopyramide, flecainide, moricizine, procainamide, propafenone, quinidine, or sotalol.  The results of the AFFIRM trial indicate that managing atrial fibrillation with rhythm control strategy offers no survival advantage over the rate control strategy². 

Atrial fibrillation is one of the most common arrthmias and a major cause of ischemic stroke⁵.  The concern that arises is that during atrial fibrillation, is that there is a lack of complete heart contraction which can increase the possibility of blood clot formation in the heart, thus restoring a normal heart rhythm by cardioversion can dislodge the blood clot from the heart and lead to a heart attack or stroke.  This risk could be prevented by anticoagulation¹. 

Amiodarone Cardioversion Stroke Risk and Need for Anticoagulation

Amiodarone mechanism includes sodium, potassium, calcium channel, and noncompetitive b-blocking to maintain sinus rhythm, though serious adverse effects including increased stroke risk should be considered before initiating therapy⁵. 

In 1990, a case report of stroke after amiodarone cardioversion was reported in a 66 year old female patient with symptomatic paroxysmal atrial fibrillation for a duration of 5 weeks. The patient was not on any prophylactic antiarrhythmics, had hypertension, and not had previous ischemic heart disease or transient ischemic attacks. She was taking propranolol 160 mg daily for hypertension and eleven days after starting amiodarone the patient felt her heart rhythm change and had an improvement in symptoms.  Four hours later she developed sudden onset numbness and right-sided weakness with computed tomography confirming cerebral infarct³.

More recently, the 2013 FinCV study, focused on thromboembolic complications after cardioversion of acute atrial fibrillation lasting less than 48 hours. Embolic complications were evaluated during the 30 days after 5,116 successful cardioversions in 2,481 patients without oral anticoagulation or peri-procedural heparin therapy.  The results of the study indicate that there were 38 (0.7%; 95% confidence interval [CI]: 0.5% to 1.0%) definite thromboembolic events within 30 days (median 2 days, mean 4.6 days) after cardioversion which included 31 strokes. Additionally, 4 patients experienced a transient ischemic attack after cardioversion.  Independent predictors of definite embolic events included age (odds ratio [OR]: 1.05; 95% CI: 1.02 to 1.08), female sex (OR: 2.1; 95% CI: 1.1 to 4.0), heart failure (OR: 2.9; 95% CI: 1.1 to 7.2), and diabetes (OR: 2.3; 95% CI: 1.1 to 4.9).  The lowest risk was in no heart failure and age < 60 years patients (0.2%) and the highest risk of thromboembolism was found in heart failure and diabetes patients (9.8%).  The results show that even without anticoagulation embolic events are rare (<1%) within 30 days after cardioversion of acute atrial fibrillation with most embolic events occurring within 3 to 4 days after cardioversion, but the risk increases with increasing age, female sex, heart failure, and diabetes.  Results indicate that both the CHADS and CHADS2VASc were predictive for thromboembolism⁴. 

Published in 2015, a nationwide population-based cohort study in Taiwan of 7548 patients with atrial fibrillation were divided into two groups according to whether they received amiodarone.  Patient with a history of stroke who received amiodarone before the index date or the following 30 days, or those who experienced stroke within 30 days of receiving amiodarone were excluded.  The risk of ischemic stroke with amiodarone was 1.81 times (95% confidence interval [CI] 1.52–2.16), 1.79 times (95% CI 1.50–2.14), and 1.78 times(95% CI 1.49–2.13) higher without amiodarone in atrial fibrillation patients as shown by the statistical analysis of crude, Model 1, and Model 2 Cox proportional hazard regression models.  Additionally, the risk of ischemic stroke with amiodarone was higher in female patients and patients aged < 65 years, without comorbidities, who were also taking digoxin or had a low CHA2DS2VASc score.  The study concluded that treatment with amiodarone for atrial fibrillation is associated with an increased stroke risk and that digoxin and amiordarone increased the risks of stroke and the two drugs should be avoided together⁵. 

The Yapa 1990 case report highlighted that the risk of cerebral embolization after stroke is possible and anticoagulation should be started prior to treatment of atrial fibrillation with cardioversion³.  The AFFIRM trial also indicated that ischemic strokes occurred in 77 and 80 patients in the rate-control and rhythm-control groups, respectively (annual rate of approximately 1 percent per year in each group), with majority of strokes occurring in patients who had stopped warfarin or who had a subtherapeutic INR.  The rhythm control group included patients taking amiodarone and the trial suggested that the adverse effects of amiodarone might increase with longer use and continuous anticoagulation is recommended in atrial fibrillation patients with risk factors for stroke even when sinus rhythm is restored².  The Chen et al 2015 trial reported that antiplatelet agents and warfarin had a similar protective effect in decreasing the stroke risk of amiodarone and furthermore mentioned that to decrease stroke risk, atrial fibrillation patients receiving amiodarone should also receive oral anticoagulation therapy with warfarin or antiplatelet agents based on the CHA2DS2VASc score⁵.

The ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation provide the following anticoagulation recommendations for prevention of thromboembolism in patients with atrial fibrillation undergoing cardioversion.  Class 1 guidelines are as follows:

·         patients with atrial fibrillation of 48 hours or longer or for unknown duration of atrial fibrillation, anticoagulation is recommended at least 3 weeks prior to and 4 weeks after cardioversion regardless of electrical or chemical cardioversion method used (Level of Evidence B);

·         patients with atrial fibrillation more than 48 hours that require immediate cardioversion due to hemodynamic instability, heparin is to be administered concurrently by IV bolus and then a continuous infusion dose adjusted to prolong the aPTT 1.5 to 2x reference control, additionally, oral anticoagulation (INR 2.0 to 3.0) should be continue for at least for 4 weeks in patients with elective cardioversion (Level of Evidence: C); 

·         patients with atrial fibrillation less than 48 hours associated with hemodynamic instability (angina pectoris, MI, shock, or pulmonary edema), cardioversion should be performed immediately without delay for anticoagulation initiation (Level of Evidence: C) ⁶. 

Summary

Based on the limited evidence, it can be concluded that amiodarone cardioversion is associated with a risk of stroke though the risk can vary depending on patient factors.  Research studies and ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation recommend anticoagulation to prevent thromboembolism in patients with atrial fibrillation undergoing cardioversion.  As always, choice between anticoagulation should be continued to be based on patient factors.  

Pediatrics Review

Common Antidotes

Common Antidotes

Drug	Antidotes
Acetaminophen	acetylcysteine
Alcohol	thiamine
Anticholinesterase (insecticides)	atropine, pralidoxime
Anticholinergics	physostigmine
Benzodiazepine	flumazenil
Beta blockers	calcium chloride, epinephrine, glucagon
Calcium blockers	calcium chloride, glucagon
Carbon monoxide	hyperbaric, oxygen
Cyclophosphamide	mesna
Cyanide	amyl nitrate, sodium nitrate, sodium thiosulfate
Digoxin	digoxin immune fab
Dopamine	phenotolamine
Extrapyrimidal symptoms	diphenhydramine
Ethylene glycol	fomepizole, ethanol
Heroin	naloxone, nalmefene
Heparin	protamine sulfate
Iron	deferoxamine
Lead	dimercapol, edetate calcium, disodium
Methemoglobinemia	methylene blue
Methotrexate	leucovorin
Neuromuscular blockade	anticholinesterase
Potassium	albuterol inhaler, insulin/glucose, NaHCO3, kayexalate
Serotonin syndrome	cyproheptadine
Sulfonylurea hypoglycemic	octreotide
Theophylline	pyridoxine
Warfarin	phytonadione, vitamin K

Weight Loss and Gain Medications

Weight Loss Medications

Use with reduced-calorie diet and increased physical activity

Contrave (naltrexone/bupropion)

·         Naltrexone is an opiod antagonist

·         BMI

o   30 kg/m² or greater (obese) or

o   27 kg/m² or greater (overweight) + comorbidity

§  Hypertension

§  Type 2 diabetes mellitus

§  Dyslipidemia

·         4-week dose titration schedule

·         ADR – suicidality, neuropsychiatric reactions

·         Administration

o   NOT cut, chew, or crush Contrave tablets

o   NOT take Contrave with high-fat meals à seizures

Belviq (lorcaserin)

·         Serotonin 2C receptor agonist

·         ADR - serotonin syndrome, neuroleptic malignant syndrome

·         Administration

o   with or without food

Qsymia (phentermine/topiramate)

·         Phentermine - sympathomimetic amine anorectic

·         Topiramate - antiepileptic medication

·         ADR - concentration, memory, and speech difficulties

·         Administration

o   With or without food

o   Avoid in evening à insomnia

o   Avoid alcohol à dizziness and sleepiness

o   NOT stop suddenly à seizures

Alli (orlistat)

·         Inhibits gastrointestinal lipases

·         Administration

o   3 times a day with each main meal containing fat

o   Take multivitamin with A,D,E,K

·         ADR – GI effects, gas

Evaluate response after 12 weeks

If 5% weight loss not seen à stop drug

Weight Loss Bariatric Surgery

• BMI > 35 + comorbidity (hypertension, dyslipidemia, type 2 diabtes)
• BMI > 40

Weight Gain Medications

• Anticonvulsants (carbamazepine, gabapentin, pregabalin, valproic acid, lithium)
• Antidepressants (phenelzine, mirtazapine, paroxetine, amitriptyline, nortriptyline)
• Antihistamines (H1 blockers - cetirizine)
• Antihypertensives (atenolol, propanolol)
• Vasodilators (minoxidil)
• Antipsychotics (chlorpromazine, clozapine, iloperidone, olanzapine, quetiapine, risperidone)
• Corticosteroids 
• Hormonals (medroxyprogesterone, megestrol)
• Hypoglycemic (insulin, sulfonylureas, meglitinides, thiazolidinediones)

Source:

http://www.pharmacytimes.com/contributor/anyssa-garza/2015/03/weight-loss-medications-on-the-market

Addyi (filbanserin) Drug Information

·         Background

o   HSDD 7.7 to 14% of premenopausal women in the US or 5.5 to 8.6 million individuals

o   developed by Sprout pharmaceuticals

o   approved by FDA on June 4, 2015

·         Indication

o   hypoactive sexual desire disorder (HSDD)

·         Adverse effects

o   fainting, nausea, dizziness, sleepiness, low blood pressure

·         Mechanism

o   mechanism is unknown

o   mixed agonist/antagonist effect on postsynaptic serotonergic receptors

o   5HT1A agonist and 5HT2A antagonist

·         Concerns

o   avoid with alcohol due to concerns about central nervous system depression, hypotension, syncope

o   avoid in pregnant women

o   avoid with strong or moderate CYP3A4 inhibitors

o   prior to HSDD, it was considered for antidepressant indication and though all antidepressants have a black box warning for suicides, there is no sign of increase risk with filbanserin

·         Pharmacokinetics

o   peak levels reached in 45 to 60 minutes of administration

o   peak levels are delayed by 1 to 3 hours with meal

o   terminal elimination half-life is 12 hours

o   taking with high fat high calorie meal increases exposure 50%

o   administration with CYP3A4 inhibitors (ketoconazole, fluconazole) increases filbanserin 4.5 and 7 times, respectively

o   hormonal contraceptives are weak inhibitors of CYP3A4, but increase filbanserin 40%

Source:
Pharmacy Times. What to Know About “Female Viagra” Backed by FDA Panel.  http://www.pharmacytimes.com/news/what-to-know-about-female-viagra-backed-by-fda-panel#sthash.UW4UXYXR.dpuf

Drug Information Question

Question: Patient asked whether her Metformin interacted with an over-the-counter medication she was taking. 

Answer: Based on researching the information in Micromedex, it was found that there was no interaction of concern. To further understand possible over-the-counter medications interactions with Metformin, I read the journal article Drug Interactions of Medications Commonly Used in Diabetes and learned that the major OTC interaction of metformin is cimetidine.  Cimetidine causes a 60% increase in peak metformin plasma levels. The incidence of metformin-induced lactic acidosis may reach 0.084 cases per 1000 patient-years, with 50% of the cases being fatal.  Other adverse effects associated with metformin are upset stomach, B12 deficiency, and headache.

Source:

Metformin.  Drug Interactions.  Micromedex Solutions.  Truven Health Analytics, Inc. Greenwood Village, CO.  Available at: http://www.micromedexsolutions.com.  Accessed May 22, 2015.

Triplitt, C. "Drug Interactions of Medications Commonly Used in Diabetes." Diabetes Spectrum (2006):19(4); 202-11.

Drug Information Question

Question – Patient receives a prescription for Lamisil (terbinafine) 250mg for 10days and is inquiring when he may be allowed to drink alcohol again as he plans to attend a wedding on day 11.

Answer – Lamasil has a half-life of 22 to 26 hours with the half-life of 200 to 400 hours from skin and adipose tissue. Half-life is the amount of time needed to decrease the amount of drug in the body 50%. It usually takes 5 half-lives for the drug to be eliminated from the body close to 100%. With a half-life of 24 hours it would take approximately 5 days for terbinafine to be eliminated from the body. It would be best to wait 5 days before consuming alcohol after finishing the course of terbinafine. I called Novartis and they recommended not drinking alcohol with this product and they said they could not make a recommendation for after the patient stopped taking the medication.

Source:

Terbinafine hydrochloride.  DrugPoints Summary.  Micromedex 2.0.  Truven Health Analytics, Inc. Greenwood Village, CO.  Available at: http://www.micromedexsolutions.com.  Accessed June 16, 2015.

Key Drug Interactions

Key Drug Interactions

·         Serotonin syndrome

o   Mental status changes, agitation, diaphoresis, tachycardia, death

o   monoamine oxidase inhibitor (MAOI) - phenelzine or tranylcypromine sulfate

o   dextromethorphan, meperidine, and SSRI such as fluoxetine

o   stop fluoxetine 5 weeks before MAOI due to long half-life of metabolite norfluoxetine

o   wait 2 after MAOI ends and SSRI begins 

·         Digoxin and Quinidine

o   Increase in digoxin levels

o   Quinidine displaces digoxin from binding sites and leading to a decreased Vd of digoxin

o   Quinidine decreases renal and nonrenal excretion of digoxin

·         Sildenafil and Isosorbide mononitrate

o   Hypotension due to sildenafil being a PDE5 inhibitor and nitrates increase cGMP

·         Potassium (chloride, bicarbonate, citrate, acetate, gluconite, and iodide) and potassium sparing diuretics (spironolactone, amiloride, triamterene)

o   Leads to hyperkalemia, cardiac failure, and death especially in patients in renal impairment

·         Clonidine and Propanolol

o   Rebound hypertension when suddenly stopping clonidine

o   Clonidine is a central alpha-2 adrenergic agonist that causes a decrease in NE

o   Alpha-1 receptors then become sensitized because of less norepinephrine

o   With suddenly withdrawn a large increase in norepinephrine occurs leading to vasoconstriction by the sensitized alpha1 receptors

o   Body cannot compensate because the beta-2 receptors are blocked

·         Warfarin and NSAID (diflunisal, ketoprofen, piroxicam, sulindac, diclo-fenac, and ketorolac)

o   increase the risk of GI bleeding

o   acetaminophen or nonacetylated salicylates (magnesium salicylate or salsalate) is an alternative

·         Theophylline and Ciprofloxacin

o   Increase in theophylline levels

o   Theophylline is metabolized by CYP1A2

o   Ciprofloxacin, clarithromycin, erythromycin, fluvoxamine, and cimetidine inhibit CYP1A2

o   levofloxacin or ofloxacin is an alternative

·         Pimozide and Ketoconazole

o   Prolong QT interval and ventricular arrhythmias (torsades de pointes)

o   Pimozide is metabolized by CYP3A4

o   Ketoconazole, fluconazole inhibit CYP3A4

o   Terbinafine is safer

·         Methotrexate and Probenecid or Penicillins or Salicylates

o   Increase methotrexate levels

o   Probenecid inhibits renal secretion

o   methotrexate toxicity include diarrhea, vomiting, diaphoresis, renal failure, and death

o   alternatives include acetaminophen not salicylates or NSAIDS (celecoxib okay, rofexcoxib NOT okay)

·         Bromocriptine and Pseudoephedrine

o   peripheral vasoconstriction, ventricular tachycardia, seizures, and possibly death

o   Bromocriptine dopamine agonist for Parkinson’s (first line therapy is bromocriptine or other dopamine agonist such as ropinirole, pramipexole, or pergolide

o   Avoid all sympathomimetics with bromocriptine

Source: http://www.pharmacytimes.com/publications/issue/2002/2002-11/2002-11-7010

Theophylline

Theophylline

·         xanthine derivative

·         treats asthma and stable COPD to relax the bronchial smooth muscle

·         serum theophylline concentration of 10–20mg/L 

·         Symptoms of theophylline toxicity

o   Nausea

o   Vomiting

o   Gastric irritation

o   Diarrhea

o   Palpitations

o   Tachycardia

o   Arrhythmias

o   Headache

o   Central nervous system stimulation

o   Insomnia

o   Convulsions

·         Metabolized in the liver by CYP1A2

o   Cirrhosis, congestive heart failure, and hepatitis reduce theophylline clearance

·         Common drug interactions

o   Benzodiazepines

§  theophylline antagonizes the sedative and anxiolytic effects of benzodiazepines

o   H2-receptor antagonists

§  theophylline concentrations are increased by cimetidine

§  famotidine, nizatidine, and ranitidine do not interact

o   Ciprofloxacin

§  theophylline concentrations are increased

o   Erythromycin

§  theophylline concentrations are increased because theophylline clearance is reduced

o   Levothyroxine

§  theophylline concentrations are increased with hypothyroidism treatment

o   Methotrexate

§  theophylline concentrations are increased because theophylline clearance is reduced

§  might reduce methotrexate-induced neurotoxicity and methotrexate efficacy

o   Phenytoin

§  theophylline concentrations are decreased because increases the clearance of theophylline

·         Age

o   neonates and elderly have reduced theophylline clearance

·         Smokers

o   smokers need higher theophylline doses than non-smokers

o   tobacco smoke induces CYP1A2

o   smoking cessation results in increase in serum theophylline concentrations

o   reduce theophylline dose with smoking cessation

·         Adverse effects

o   risk of QT-interval prolongation with theophylline AND citalopram or fluoxetine together

o   low potassium, magnesium or calcium can cause QT prolongation

Source:

http://www.pharmaceutical-journal.com/learning/learning-article/theophylline-interactions/20065570.article

http://www.rxkinetics.com/manual.html